Glutathione modified low molecular weight PEI for highly improved gene transfection ability and biocompatibility

The efficient delivery of therapeutic genes remains a major challenge in realizing a feasible gene-based treatment. Herein, a versatile oligopeptide, glutathione, was introduced to construct novel non-viral cationic gene vectors. Reduced/oxidized forms of glutathione (GSH/GSSG) and relevant amino ac...

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Bibliographic Details
Published in:New journal of chemistry 2019-07, Vol.43 (3), p.1219-12117
Main Authors: Zhan, Yu-Rong, Yu, Qing-Ying, Zhang, Ji, Liu, Yan-Hong, Xiao, Ya-Ping, Zhang, Ju-Hui, He, Xi, Yu, Xiao-Qi
Format: Article
Language:English
Subjects:
Amino acids
Biocompatibility
Cationic polymerization
Crosslinking
Deoxyribonucleic acid
DNA
Efficiency
Flow cytometry
Glutathione
Low molecular weights
Molecular weight
Nanoparticles
Polymers
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Summary:The efficient delivery of therapeutic genes remains a major challenge in realizing a feasible gene-based treatment. Herein, a versatile oligopeptide, glutathione, was introduced to construct novel non-viral cationic gene vectors. Reduced/oxidized forms of glutathione (GSH/GSSG) and relevant amino acids (Glu, Cys, and Gly) were used to modify low molecular weight PEI through surface modification or crosslinking. These polymers could bind well and condense DNA into spherical nanoparticles, which were stable in the presence of serum. The disulfide bonds within the crosslinked polymer GSSG-PEI may facilitate polymer degradation and DNA release under a reductive environment. In vitro transfection experiments reveal that the modification could largely improve the gene transfection efficiency of low molecular weight PEI, especially in the presence of serum. In HeLa cells, GSSG-PEI could even give up to 150 times higher efficiency than PEI 25 kDa. TEM and serum concentration effect assay also demonstrate the good serum tolerance of the polymers. Flow cytometry results show that GSSG-PEI might induce cellular uptake with higher efficiency than PEI 25 kDa, especially in the presence of serum. Results reveal that GSSG is a good candidate for the crosslinking of small cationic molecules to form polymeric gene vectors with improved transfection efficiency and biocompatibility. A versatile oligopeptide, glutathione, was introduced to construct novel cationic gene vectors with further excellent transfection efficiency and serum tolerance.
ISSN:1144-0546
1369-9261
DOI:10.1039/c9nj02396h